42 results about "DKK1" patented technology

Provided herein is a method for gene expression profiling multiple myeloma patients into distinct subgroups via DNA hybridization and hierarchical clustering analysis of the hybridization data where the results may further be used to identify therapeutic gene targets. Also provided is a method for controlling bone loss in an individual via pharmacological inhibitors of DKK1 protein. In addition provided herein is a method for diagnosing multiple myeloma using a 15-gene model that classifies myeloma into groups 1-7.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3 / FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease.

Gene expression profiling reveals four distinct subgroups of multiple myeloma that have significant correlation with various clinical characteristics. Diagnosis for multiple myeloma (and possibly monoclonal gammopathy of undetermined significance) based on differential expression of 14 genes, as well as prognosis for the four subgroups of multiple myeloma based on the expression of 24 genes are established. A 15-gene model that classifies myeloma into 7 groups is also reported. Gene expression profiling also allows placing multiple myeloma into a developmental schema parallel to that of normal plasma cell differentiation. Development of a gene expression- or developmental stage-based classification system for multiple myeloma would lead to rational design of more accurate and sensitive diagnostics, prognostics and tumor-specific therapies for multiple myeloma.

The present invention provides antibodies and immunologically functional fragments thereof that specifically bind DKK1 polypeptides. Methods for preparing such antibodies or fragments thereof as well as physiologically acceptable compositions containing the antibodies or fragments are also provided. Use of the antibodies and fragments to treat various diseases are also disclosed.

The present invention relates to a method of culturing primitive-like macrophages from stem cells, a kit when used in the method thereof and uses of the primitive like macrophage for in-vitro disease models and for screening compounds for therapy. One embodied culture method comprises contacting and incubating embryonic stem cells or induced pluripotent stem cells with a serum-free culture media comprising a GSK3 inhibitor to differentiate stem cells into cells of the mesoderm lineage, followed by incubation with a culture media comprising Dickkopf-related protein 1 (DKK1) to differentiate the mesoderm into cells of hematopoietic lineage, maturing hematopoietic cells and incubating these cells with a culture media comprising M-CSF to drive differentiation into primitive-like macrophages. Another embodiment comprises incubating the stem cells with serum-free culture media comprising FGF2 and BMP4 to induce differentiation into cells of the mesoderm lineage, followed by incubating the cells with a culture media comprising FGF2, BMP4, Activin A and VEGF to differentiate the cells of the mesoderm lineage into cells of the hematopoietic cell lineage, maturing the cells of the hematopoietic cell lineage and lastly, incubating the matured hematopoietic cells with culture media comprising M-CSF to drive the differentiation of hematopoietic cells into primitive-like macrophages.

The invention discloses a kit for juvenile osteoporosis detection. Through gene comparison, the fact that compared with a DKK1 gene in the normal people group, a juvenile form osteoporosis patient has the obvious mutant site is discovered, and the obvious mutant site is the 721 site. Through detecting the mutant site, particularly through the pair of provided specific primer pair, whether the people has the juvenile form osteoporosis symptom or not can be specifically identified. Compared with the prior art, the detection method has the advantages that the detection is convenient; accuracy and high speed are realized; the kit is suitable for being popularized and used.

The invention discloses a kit for detecting juvenile osteoporosis. According to the kit, an obvious mutant site which is a site 1020 is discovered to exist in a DKK1 gene in a patient suffering from the juvenile osteoporosis and a normal crowd through genetic comparison. Through detecting the mutant site, particularly provided one pair of specific primer pairs, a human body which suffers from the juvenile osteoporosis can be specifically identified. Compared with the method in the prior art, a detection method has the advantages of being quick for detection, accurate and quick, and is suitable to popularize and use.

The present invention provides antibodies and immunologically functional fragments thereof that specifically bind DKK1 polypeptides. Methods for preparing such antibodies or fragments thereof as well as physiologically acceptable compositions containing the antibodies or fragments are also provided. Use of the antibodies and fragments to treat various diseases are also disclosed.